In Vitro Modeling of Human Germ Cell Development Using Pluripotent Stem Cells

Yuncheng Zhao; Shicheng Ye; Dongli Liang; Pengxiang Wang; Jing Fu; Qing Ma; Ruijiao Kong; Linghong Shi; Xueping Gong; Wei Chen; Wubin Ding; Wenjing Yang; Zijue Zhu; Huixing Chen; Xiaoxi Sun; Jun Zhu; Zheng Li; Yuan Wang

Stem Cell Reports (Feb 2018)

In Vitro Modeling of Human Germ Cell Development Using Pluripotent Stem Cells

Yuncheng Zhao,
Shicheng Ye,
Dongli Liang,
Pengxiang Wang,
Jing Fu,
Qing Ma,
Ruijiao Kong,
Linghong Shi,
Xueping Gong,
Wei Chen,
Wubin Ding,
Wenjing Yang,
Zijue Zhu,
Huixing Chen,
Xiaoxi Sun,
Jun Zhu,
Zheng Li,
Yuan Wang

Affiliations

Yuncheng Zhao: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China
Shicheng Ye: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China
Dongli Liang: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China
Pengxiang Wang: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China
Jing Fu: Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
Qing Ma: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China
Ruijiao Kong: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China
Linghong Shi: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China
Xueping Gong: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China
Wei Chen: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China
Wubin Ding: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China
Wenjing Yang: Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Zijue Zhu: Department of Andrology, Urologic Medical Center, Shanghai Key Lab of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China
Huixing Chen: Department of Andrology, Urologic Medical Center, Shanghai Key Lab of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China
Xiaoxi Sun: Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
Jun Zhu: Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Zheng Li: Department of Andrology, Urologic Medical Center, Shanghai Key Lab of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China
Yuan Wang: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China; Department of Animal Science, Michigan State University, Lansing, MI 48824, USA; Corresponding author

Journal volume & issue: Vol. 10, no. 2
pp. 509 – 523

Abstract

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Summary: Due to differences across species, the mechanisms of cell fate decisions determined in mice cannot be readily extrapolated to humans. In this study, we developed a feeder- and xeno-free culture protocol that efficiently induced human pluripotent stem cells (iPSCs) into PLZF+/GPR125+/CD90+ spermatogonium-like cells (SLCs). These SLCs were enriched with key genes in germ cell development such as MVH, DAZL, GFRα1, NANOS3, and DMRT1. In addition, a small fraction of SLCs went through meiosis in vitro to develop into haploid cells. We further demonstrated that this chemically defined induction protocol faithfully recapitulated the features of compromised germ cell development of PSCs with NANOS3 deficiency or iPSC lines established from patients with non-obstructive azoospermia. Taken together, we established a powerful experimental platform to investigate human germ cell development and pathology related to male infertility. : In this article, Wang and colleagues established a feeder- and xeno-free system to robustly induce human pluripotent stem cells (PSCs) into spermatogonia-like cells. This chemically defined induction protocol faithfully recapitulated the features of compromised germ cell development of PSCs with NANOS3 deficiency or iPSC lines established from patients with non-obstructive azoospermia. Keywords: pluripotent stem cells, spermatogonia, infertility, non-obstructive azoospermia

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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